Large Scale Synthesis of the High Quality Indoloquinone Antitumor Agent EO9 via [Bis(trifluoroacetoxy)iodo]benzene Oxidation of 4-Aminoindole

Synthesis

Volumn , Issue 5, 1996, Pages 633-636

  Kinugawa, Masahiko ^a   Masuda, Yoshiaki ^a   Arai, Hitoshi ^a   Nishikawa, Hiroshi ^a   Ogasa, Takehiro ^a   Tomioka, Shinji ^a   Kasai, Masaji ^a  

^a KYOWA HAKKO KOGYO CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

5 (1 AZIRIDINYL) 3 HYDROXYMETHYL 2 (3 HYDROXY 1 PROPENYL) 1 METHYL 4,7 INDOLEDIONE; ANTINEOPLASTIC AGENT; INDOLE DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0029899188     PISSN: 00397881     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-1996-4270     Document Type: Article

References (11)

1. Oostveen, E. A.; Speckamp, W. N. Tetrahedron 1987, 43, 255.
2. Speckamp, W. N.; Oostveen, E. A. PCT Int. Appl. WO 87/06227, 1987; Chem. Abstr. 1988, 109, 22842.
3. Schellens, J. H. M.; Planting, A. S. T.; Vanacker, B. A. C.; Loos, W. J.; Deboerdennert, M.; Vanderburg, M. E. L.; Koier, I.; Krediet, R. T.; Stoter, G.; Verweij, J. J. Nat. Cancer Inst. 1994, 86, 906 and references cited therein.
4. Cotterill, A. S.; Moody, C. J.; Roffey, J. R. A. Tetrahedron 1995, 51, 7223.
5. Kinugawa, M.; Arai, H.; Nishikawa, H.; Sakaguchi, A.; Ogasa, T.; Tomioka, S.; Kasai, M. J. Chem. Soc., Perkin Trans. 1, 1995, 2677.
6. Moser, W.; Howie, R. A. Inorg. Phys. Theor. J. Chem. Soc. A 1968, 3039.
7. Barret, R.; Daudon, M. Tetrahedron Lett. 1990, 31, 4871.
8. The yield of the conventional Fremy's salt oxidation of 3 was about 70-80%.
9. +). Found: 331.1491.
10. ARBOCEL® BWW 40 is commercially available from J. Rettenmaier & Sohne Co., Ltd., Germany.
11. Allen, C. F. H.; Spangler, F. W.; Webster, E. R. Org. Synth. Coll. Vol. 4, 433 and the preparation of aq ethylenimine is described below; 10 M NaOH (2.5 L, 6.25 mol) was added to 2-amino-ethylhydrogen sulfate (882 g, 25.0 mol), and the mixture was refluxed for 1 h. Fractional distillation gave a solution of ethylenimine. Each fraction volume was 50 mL and their concentrations were 18.2 M (bp 75-92°C), 11.3 M (bp 92-97°C) and 4.7 M (bp 97-100°C) (total 3.42mol, 55% yield). Concentrations were determined as follows: To the ethylenimine solution (100 μL)in MeOH (10 mL) was added phenyl isocyanate (300 μL) in a ice bath. The reaction mixture was stirred for 30 min in the ice bath to afford 1,1-ethano-3-phenylurea. The concentration of the compound was determined by HPLC with benzophenone as the internal standard.